Primary endpoints in randomized controlled trials for older adults with cancer: A scoping review

Older adults represent a growing proportion of patients with cancer. However, confirmatory randomized controlled trials (RCTs) continue to rely primarily on tumor-based endpoints such as overall survival (OS), which may overlook outcomes particularly important to older adults, including quality of life (QOL), functional status, and treatment tolerance. This review aimed to systematically characterize the primary endpoints used in confirmatory RCTs enrolling adults aged ≥65 years and to evaluate how novel endpoints reflecting patient priorities were defined and analyzed.

PubMed, CINAHL, and the Cochrane Library were searched for English-language confirmatory RCTs exclusively enrolling adults aged ≥65 years with cancer and reporting a primary endpoint (up to January 19, 2024). Endpoints were classified as conventional (tumor-based) or novel (non-tumor-based). Data were extracted on endpoint definitions, measurement tools, and statistical approaches.

Of 822 records identified, 66 RCTs met the eligibility criteria, yielding 71 primary endpoints. Conventional outcomes predominated (n = 53; 74.6%), with OS being the most frequent, followed by progression-free survival and disease-free survival. Novel endpoints (n = 18; 25.3%) included health-related QOL (HR-QOL), toxicity, geriatric assessment-based measures, composite endpoints, and patient satisfaction. HR-QOL was most commonly assessed using the European Organization for Research and Treatment of Cancer QLQ-C30. Definitions of toxicity and functional decline varied across studies. Variance assumptions were rarely reported, and minimal clinically important differences were inconsistently applied. Additional endpoints, such as quality-adjusted survival, overall treatment utility, and disability-free survival, were infrequently reported.

Survival remains the predominant endpoint in confirmatory RCTs involving older adults with cancer, while patient-relevant outcomes are inconsistently incorporated. Addressing these gaps may facilitate more patient-centered trial designs and improve the real-world applicability of research findings for the aging cancer population.